Tetragenococcus lactic acid bacteria, composition for oral intake, composition for antidepressant, and composition for antianxiety agent

Abstract

To provide a lactic acid bacterium belonging to the genus Tetragenococcus, easy to produce because of simple culture, requiring neither expensive production facilities nor complicated production processes, being an inexpensive, stable and safe food material (food component), and capable of increasing serotonin in the brain, dopamine in the brain, or both of them.SOLUTION: A Tetragenococcus lactic acid bacterium capable of increasing at least one selected from the group consisting of brain serotonin and brain dopamine.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to Tetragenococcus lactic acid bacteria, oral compositions, antidepressant compositions, and anti-anxiety compositions. More specifically, the present invention relates to Tetragenococcus lactic acid bacteria, which are inexpensive, stable, and safe food materials (food ingredients) and have the ability to increase brain serotonin (5-HT), brain dopamine (DA), or both, and oral compositions, antidepressant compositions, and anti-anxiety compositions containing the same. [Background technology]

[0002] As society becomes more complex, modern people are exposed to a lot of stress. If this stress is not resolved and left untreated, it can lead to psychological reactions such as depression, anxiety, fatigue, anger, and mood changes, as well as physiological reactions such as increased blood pressure and pulse rate. If these reactions continue, depression, anxiety, sleep disorders, etc. can develop, causing personal, familial, and societal losses and a decline in the quality of life of individuals.

[0003] In fact, a patient survey conducted by the Ministry of Health, Labor and Welfare has shown that the number of patients with neurotic disorders, stress-related disorders, somatoform disorders, and mood (affective) disorders (including bipolar disorder) is increasing year by year, becoming a social problem.

[0004] In depression, it is thought that symptoms such as anxiety, melancholy, loss of motivation, loss of interest, and impatience appear due to a deficiency of the neurotransmitters monoamines (5-HT, norepinephrine (NA), and DA), and this has long been proposed as the "monoamine hypothesis" (see non-patent literature 1 and 2).

[0005] Antidepressants used to treat depression are thought to improve symptoms by increasing the extracellular concentration of these neurotransmitters in the brain (concentration in the synaptic cleft).

[0006] Currently, antidepressants with various mechanisms are used to treat depression, including classical tricyclic antidepressants, tetracyclic antidepressants, selective 5-HT reuptake inhibitors (SSRIs), 5-HT / NA reuptake inhibitors (SNRIs), NA agonist / specific 5-HT agonist antidepressants (NaSSAs), and selective NA reuptake inhibitors (see Non-Patent Document 3).

[0007] SSRIs (such as paroxetine) are drugs that primarily increase extracellular 5-HT concentrations, and by increasing 5-HT they also improve anxiety symptoms, so they are used to treat not only depression but also anxiety disorders.

[0008] Furthermore, while antidepressants (SSRIs, SNRIs, NaSSAs, etc.) that target the neurotransmitters 5-HT and NA have been mainstream up until now, development of 5-HT, NA, and DA reuptake inhibitors that also target DA has recently been progressing. These are expected to be effective for symptoms thought to be related to DA, such as "not being able to enjoy anything," which have not been effective with conventional antidepressants.

[0009] Here, 5-HT acts on the receptor to transmit information. Currently, serotonin receptors (5-HT receptors) are classified into seven families, with at least 14 subtypes.

[0010] The serotonin 7 receptor (5-HT7), discovered in 1993, belongs to this family and has attracted considerable attention as a valuable new drug target (see Non-Patent Document 4). SB 269970, a selective 5-HT7 receptor antagonist, has been reported to exhibit anxiolytic and antidepressant-like activity in animal studies using rodents (see Non-Patent Document 5).

[0011] Furthermore, the incidence of insomnia in depression is as high as 84.7% (see Non-Patent Document 6), and "insomnia almost every day" is included as one of the conditions in the diagnostic criteria for depression in the "DSM-5 Diagnostic and Statistical Manual of Mental Disorders" (see Non-Patent Document 7).

[0012] Orexin is one of the neurotransmitters that regulates wakefulness and sleep. When orexin acts on its receptor (orexin receptor), it activates the wakefulness system and maintains wakefulness. When this wakefulness system is overactive, symptoms such as insomnia are likely to occur. Conversely, suppressing the activity of this wakefulness system can promote the transition of the brain from a wakeful state to a sleep-inducing state. From this perspective, an orexin receptor antagonist (lemborexant) is used as a sleep-inducing drug (see Non-Patent Document 8).

[0013] However, various side effects have been reported for the above antidepressants. For example, SSRIs have been associated with nausea, headache, and irritability, while SNRIs have been associated with tremor, tachycardia, erectile and ejaculatory disorders. Furthermore, there have been several reported cases in which the administration of multiple types of antidepressants results in an increase in side effects compared to the administration of a single drug (see Non-Patent Document 9).

[0014] Furthermore, the antidepressants and anti-anxiety drugs mentioned above can only be used after a doctor's diagnosis and prescription, making them difficult to use in terms of preventing mood disorders such as depression and / or anxiety disorders.

[0015] It has been reported that the intake of tryptophan, a precursor of 5-HT, is effective in enhancing the effects of antidepressants (see Non-Patent Document 2). This suggests that increasing the 5-HT content in the brain is a promising option for treating depression, and it is currently widely recommended that depressed patients take tryptophan from their diet.

[0016] Furthermore, food-derived compositions that increase brain 5-HT and / or brain DA include kale, propolis, or extracts thereof (see Patent Document 1), lactoferrin (see Patent Document 2), and bifidobacteria (see Patent Document 3).

[0017] Furthermore, Lactobacillus fermentum GKF3 (see Patent Document 4) has been reported as a food-derived material that increases brain 5-HT and / or brain DA. [Prior art documents] [Patent documents]

[0018] [Patent Document 1] Japanese Patent Application Laid-Open No. 2003-300892 [Patent Document 2] Japanese Patent Application Publication No. 2019-156814 [Patent Document 3] Japanese Patent Application Laid-Open No. 2017-175949 [Patent Document 4] Japanese Patent Publication No. 2020-80861 [Non-patent literature]

[0019] [Non-Patent Document 1] Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965 122(5):509-22. doi: 10.1176 / ajp.122.5.509. [Non-patent document 2] Coppen A. The biochemistry of affective disorders. Br J Psychiatry 1967 113(504):1237-64. [Non-patent document 3] Kazuyuki Shimada et al. Today's Therapeutic Drugs 2022: Commentary and Handbook. pp. 878-887 Nanzando [Non-patent document 4] Terron, JA Idrugs. The 5HT7 receptor: A target for novel therapeutic avenues 1998 1(3):302-310. [Non-Patent Document 5] Anna Wesolowska, Agnieszka Nikiforuk, Katarzyna Stachowicz, Ewa Tatarczynska. Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression. Neuropharmacology. 2006 51(3):578-586. [Non-patent document 6] Sunderajan P, Gaynes BN, Wisniewski SR, et al. Insomnia in patients with depression: a STAR*D report. CNS spectrums2010; 15: 394-404. [Non-Patent Document 7] Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. ed. Arlington, VA: American Psychiatric Association; 2013. [Non-patent document 8] Koei, Michinori, Koyama, Noriyuki, Nishida, Maika, Muramoto, Kenzo. Pharmacological effects and clinical usefulness of the novel orexin receptor antagonist lemborexant (Dayvigo tablets 2.5 mg, 5 mg, 10 mg) in patients with insomnia. Folia Pharmacol. Jpn. 156, 114-119 (2021). [Non-Patent Document 9] Shigeto Yamawaki et al. Special Edition Japanese Clinical Psychiatric Syndrome I 2003: pp.370-373 Nippon Rinshosha [Non-Patent Document 10] Van A Doze 1, Robert S Papay, Brianna L Goldenstein, Manveen K Gupta, Katie M Collette, Brian W Nelson, Mariaha J Lyons, Bethany A Davis, Elizabeth J Luger, Sarah G Wood, James R Haselton, Paul C Simpson, Dianne M Perez. Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity. Mol Pharmacol. 2011 Oct;80(4):747-58. [Non-Patent Document 11] Andreas Stengel, Hiroshi Karasawa, Yvette Tache. The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior. Horm Behav. 2015 Jul; 73: 15-22. [Non-Patent Document 12] Indira Mendez-David, Denis J David, Flavie Darcet, Melody V Wu, Saadia Kerdine-Roemer, Alain M Gardier, Rene Hen. Rapid anxiolytic effects of a 5-HT4 receptor agonist are mediated by a neurogenesis-independent mechanism. Neuropsychopharmacology 2014 May;39(6):1366-78. [Non-Patent Document 13] Shelley A. Ross, John YF Wong, Jeremiah J. Clifford, Anthony Kinsella, Jim S. Massalas, Malcolm K. Horne, Ingrid E. Scheffer, Ismail Kola, John L. Waddington, Samuel F. Berkovic, John Drago. Phenotypic Characterization of an α4 Neuronal Nicotinic Acetylcholine Receptor Subunit Knock-Out Mouse. J Neurosci. 2000 Sep 1; 20(17): 6431-6441. [Non-Patent Document 14] Nicole L. Schramm, Michael P. McDonald, and Lee E. Limbird. The α2A-Adrenergic Receptor Plays a Protective Role in Mouse Behavioral Models of Depression and Anxiety. J Neurosci. 2001 Jul 1; 21(13): 4875-4882. [Non-Patent Document 15] Markus J. Schwarz & Manfred Ackenheil. The role of substance P in depression: therapeutic implications. Dialogues in Clinical Neuroscience. 2002 4(1): 21-29. Summary of the Invention [Problem to be solved by the invention]

[0020] However, Patent Documents 1 to 3 only present in vitro test results, and no data are presented on the actual in vivo increase in brain 5-HT and / or brain DA levels. Furthermore, since Lactobacillus fermentum GKF3 described in Patent Document 4 exerts its effects as a live bacterium, it requires expensive production equipment, such as fully sterilized culture equipment and freeze-dryers. Furthermore, since the bacterium is heat-sensitive, refrigerated distribution is required. Furthermore, there is a risk of contamination with other products during the manufacturing process, causing quality abnormalities, making it difficult to use at the manufacturing site. Furthermore, its effectiveness is unstable due to its susceptibility to digestive enzymes such as gastric acid and bile acid. Therefore, production is laborious and costly, and as mentioned above, its effectiveness can be unstable, resulting in various problems in terms of quality and cost.

[0021] Given the above background, there is a need for the development of inexpensive, stable, and safe food ingredients (food components) that can be taken daily as a food in place of antidepressants such as SSRIs, do not require expensive production equipment, and do not require complicated manufacturing processes.

[0022] The present invention relates to the discovery that fermentation microorganisms, specifically certain Tetragenococcus lactic acid bacteria, which are inexpensive, stable, and safe food materials (food ingredients) that do not require expensive production facilities or complicated manufacturing processes, can increase the content of 5-HT and / or DA in the brain, thereby preventing and ameliorating mood disorders such as depression and / or anxiety disorders, and can further be taken daily as a food product, serving as an alternative to antidepressants and the like. [Means for solving the problem]

[0023] According to the present invention, the following Tetragenococcus lactic acid bacteria, oral intake compositions, antidepressant compositions, and anti-anxiety compositions are provided.

[0024] [1] A lactic acid bacterium of the genus Tetragenococcus that has the ability to increase at least one selected from the group consisting of brain serotonin (brain 5-HT) and brain dopamine (brain DA).

[0025] [2] The Tetragenococcus lactic acid bacterium described in [1] above, which has the ability to exert at least one of the following functions: enhancing the expression of adrenaline receptor, alpha 1A (Adrala), suppressing the expression of serotonin 7 receptor (5-hydroxytryptamine receptor 7 (5-HT7)), suppressing the expression of orexin receptor 2 (Hcrtr2), and suppressing the expression of tachykinin receptor 1 (Tacr1).

[0026] [3] The Tetragenococcus lactic acid bacterium according to [1] above, which is a Tetragenococcus lactic acid bacterium having accession number NITE BP-02318, a Tetragenococcus lactic acid bacterium having accession number NITE P-03760, or a Tetragenococcus lactic acid bacterium having accession number NITE P-03761.

[0027] [4] A composition for oral administration, comprising the Tetragenococcus lactic acid bacteria according to any one of [1] to [3] above.

[0028] [5] A composition for use as an antidepressant, comprising the Tetragenococcus lactic acid bacteria according to any one of [1] to [3] above.

[0029] [6] A composition for an anxiolytic agent, comprising the Tetragenococcus lactic acid bacteria according to any one of [1] to [3] above. [Effects of the Invention]

[0030] The Tetragenococcus lactic acid bacteria of the present invention are easy to produce because they are easy to culture, do not require expensive production equipment, and do not require complicated production processes; they are inexpensive, stable, and safe food materials (food ingredients), and have the ability to increase brain 5-HT, brain DA, or both of these monoamines.

[0031] The oral composition of the present invention contains the Tetragenococcus lactic acid bacteria of the present invention, and is therefore easy to produce as it is simple to culture, does not require expensive production equipment, and does not require complicated manufacturing processes.It is an inexpensive, stable, and safe food material (food ingredient), and has the ability to increase brain 5-HT, brain DA, or both of these monoamines.

[0032] The antidepressant composition of the present invention contains the Tetragenococcus lactic acid bacteria of the present invention, and therefore is easy to produce as it is easy to culture, does not require expensive production equipment, and does not require complicated production processes.It is an inexpensive, stable, and safe food material (food ingredient), and has the ability to increase brain 5-HT, brain DA, or both of these monoamines, and exerts an antidepressant effect.

[0033] The anti-anxiety composition of the present invention contains the Tetragenococcus lactic acid bacteria of the present invention, and therefore is easy to produce as it is easy to culture, does not require expensive production equipment, and does not require complicated production processes.It is an inexpensive, stable, and safe food material (food ingredient), and has the ability to increase brain 5-HT, brain DA, or both, and exerts an anxiolytic effect. DETAILED DESCRIPTION OF THE INVENTION

[0034] The following describes embodiments of the present invention, but the present invention is not limited to the following embodiments. In other words, it should be understood that modifications and improvements to the following embodiments, based on the ordinary knowledge of a person skilled in the art, as long as they do not deviate from the spirit of the present invention, also fall within the scope of the present invention.

[0035] [1] Tetragenococcus lactic acid bacteria: The Tetragenococcus lactic acid bacteria of the present invention have the ability to increase at least one selected from the group consisting of brain 5-HT and brain DA.

[0036] This Tetragenococcus lactic acid bacterium is easy to culture and therefore easy to produce, does not require expensive production equipment, and does not require complicated manufacturing processes.It is an inexpensive, stable, and safe food material (food ingredient), and has the ability to increase brain 5-HT, brain DA, or both of these monoamines.

[0037] Here, when ordinary lactic acid bacteria (lactic acid bacteria that do not have salt tolerance, etc.) are commercially produced, concentration and purification of the bacterial cells and treatment of the culture medium (for example, sterilization using an autoclave or similar) are required. Furthermore, during cultivation, an environment must be maintained that prevents contamination by contaminating bacteria such as miscellaneous bacteria, which increases the effort and cost of production. On the other hand, the Tetragenococcus lactic acid bacteria of the present invention are salt-tolerant, and therefore can be cultivated in a high-salt environment in which contaminating bacteria have difficulty growing, and can be easily cultivated under conditions that suppress the growth of contaminating bacteria.

[0038] As used herein, the term "ability to increase brain 5-HT" refers to the ability to directly or indirectly increase the amount of 5-HT in the brain, or to promote the secretion of 5-HT in the brain. Furthermore, it can be said that the ability to increase the 5-HT concentration in the brain by continuously orally ingesting the Tetragenococcus lactic acid bacteria of the present invention, compared before and after ingestion, can be used to describe the ability to increase the 5-HT concentration in the brain.

[0039] Similarly, the "ability to increase brain DA" refers to the ability to directly or indirectly increase the amount of DA in the brain, or to promote DA secretion in the brain. Furthermore, it can be said that by continuously orally ingesting the Tetragenococcus lactic acid bacteria of the present invention, the DA concentration in the brain can be increased by comparing it before and after ingestion.

[0040] The Tetragenococcus lactic acid bacteria of the present invention preferably have the ability to enhance the expression of Adrala, suppress the expression of 5-HT7, suppress the expression of Hcrtr2, and suppress the expression of Tacr1, and such abilities can increase brain 5-HT and brain DA, as well as improve symptoms of depression and anxiety.

[0041] It has been reported that a deficiency of Adrala causes depression-like symptoms and anxiety. On the other hand, it has also been reported that continuous stimulation of Adrala improves these symptoms. Therefore, it is thought that increasing Adrala expression is likely to be effective in improving depression-like symptoms and anxiety (see Non-Patent Document 10).

[0042] 5-HT7 receptor antagonists have been reported to have anxiolytic and antidepressant effects, and therefore, it is thought that suppressing 5-HT7 expression is likely to be effective in improving depressive and anxiety symptoms (see Non-Patent Document 5).

[0043] Orexin receptor antagonists have hypnotic effects and are already on the market as hypnotics, so suppressing Hcrtr2 expression is likely to be effective in improving insomnia (see Non-Patent Document 8).

[0044] Tacr1 is a receptor for the neuropeptide Substance P. It has been reported that blockers of this receptor have antidepressant effects. Therefore, it is expected that reducing Tacr1 expression will be effective against depression (see Non-Patent Document 15).

[0045] Tetragenococcus lactic acid bacteria are salt-tolerant lactic acid bacteria. "Having salt tolerance" means that they have the property of being able to be cultured in a medium with a high salt concentration (specifically, a salt concentration of 11 w / v% or more).

[0046] As described above, the Tetragenococcus lactic acid bacteria are salt-tolerant lactic acid bacteria, and are easy to cultivate. Furthermore, cultivation is even easier when the growth rate is 30 times or more when cultured in a medium with a salt concentration of 12 w / v%.

[0047] The Tetragenococcus lactic acid bacteria of the present invention can be, for example, those isolated during the brewing process of miso (particularly rice miso).Specific examples of salt-tolerant lactic acid bacteria isolated during the brewing process of rice miso include the trade name "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.).

[0048] Furthermore, lactic acid bacteria "isolated during the miso brewing process" refers to salt-tolerant lactic acid bacteria that are established in the "kura," "muro," and "oke" (wood vats) used in the miso brewing process. Furthermore, it refers to lactic acid bacteria that can grow from the preparation of miso to the maturation process. These lactic acid bacteria "isolated during the miso brewing process" can also be called salt-tolerant lactic acid bacteria contained in miso (i.e., miso lactic acid bacteria), or, in other words, salt-tolerant lactic acid bacteria derived from miso (i.e., salt-tolerant lactic acid bacteria originating from miso). In the present invention, lactic acid bacteria "isolated during the miso brewing process" are not limited to those isolated during the miso brewing process, but also include those isolated during the miso brewing process and subsequently cultured (subcultured).

[0049] As described above, the Tetragenococcus lactic acid bacteria of the present invention are not particularly limited as long as they have the ability to increase at least one selected from the group consisting of brain 5-HT and brain DA, and examples include the Tetragenococcus lactic acid bacteria under accession number NITE BP-02318, the Tetragenococcus lactic acid bacteria under accession number NITE P-03760, and the Tetragenococcus lactic acid bacteria under accession number NITE P-03761. The Tetragenococcus lactic acid bacteria under accession number NITE BP-02318 is known under the trade name "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.).

[0050] The Tetragenococcus lactic acid bacteria with accession number NITE BP-02318 was deposited at the National Patent Microorganisms Depositary (NPMD) of the National Institute of Technology and Evaluation on August 3, 2016 (domestic deposit date), and was transferred to international deposit under the Budapest Treaty on September 6, 2017.

[0051] The Tetragenococcus lactic acid bacteria with accession number NITE P-03760 was deposited at the National Patent Microorganisms Depositary (NPMD) of the National Institute of Technology and Evaluation on October 11, 2022 (domestic deposit date). The Tetragenococcus lactic acid bacteria with accession number NITE P-03761 was deposited at the National Institute of Technology and Evaluation on October 11, 2022 (domestic deposit date).

[0052] The Tetragenococcus lactic acid bacteria of the present invention may be killed or live.

[0053] [1-1] Tetragenococcus lactic acid bacteria under accession number NITE BP-02318: The Tetragenococcus lactic acid bacterium, accession number NITE BP-02318, has the ability to enhance the expression of Adrala, suppress the expression of 5-HT7, suppress the expression of Hcrtr2, and suppress the expression of Tacr1.

[0054] [1-2] Tetragenococcus lactic acid bacteria under accession number NITE P-03760: The Tetragenococcus lactic acid bacteria under accession number NITE P-03760 has the ability to enhance the expression of Adrala, suppress the expression of 5-HT7, suppress the expression of Hcrtr2, and suppress the expression of Tacr1, as well as suppress the expression of 5-hydroxytryptamine receptor 4 (5-HT4) and somatostatin receptor 2 (Sstr2).

[0055] It has been reported that 5-HT4 induces depression and anxiety-like symptoms when its receptor agonist is used (see Non-Patent Document 12). Therefore, it is thought that suppressing the expression of this receptor is likely to be effective in alleviating depression and anxiety.

[0056] Somatostatin is a hormone involved in feeding, and it has been reported that somatostatin-induced feeding behavior can be suppressed by somatostatin 2 receptor antagonists (see Non-Patent Document 11). Therefore, it is thought that suppressing the expression of this receptor is likely to be effective in suppressing overeating.

[0057] [1-3] Tetragenococcus lactic acid bacteria under accession number NITE P-03761: The Tetragenococcus lactic acid bacteria, accession number NITE P-03761, has the ability to enhance the expression of Adrala, suppress the expression of 5-HT7, suppress the expression of Hcrtr2, and suppress the expression of Tacr1, as well as suppress the expression of Sstr2. Furthermore, it has the ability to enhance the expression of the ACH receptor Nicotinic Alpha 4 Subunit (CHRNA4) and the Adrenergic receptor, alpha 2A (ADRA2A).

[0058] "CHRNA4" is a subunit of the acetylcholine receptor, which is important for cognitive function. It has been reported that a deficiency of CHRNA4 induces anxiety symptoms (see Non-Patent Document 13). Therefore, it is thought that enhancing the expression of this receptor is likely to be effective in improving anxiety symptoms.

[0059] It has been reported that deficiency of ADRA2A induces depression and anxiety symptoms (see Non-Patent Document 14). Therefore, it is thought that enhancing the expression of this receptor is likely to be effective in improving depression and anxiety symptoms.

[0060] [2] Cultivation method for Tetragenococcus lactic acid bacteria: The culture conditions for the Tetragenococcus lactic acid bacteria of the present invention are not particularly limited, but they can be cultured, for example, in a medium with a salt concentration of 11 to 18 w / v%, preferably 11 to 16 w / v%, and particularly preferably 12 to 14 w / v%. Note that "w / v%" means (mass (g) / volume (100 mL))%.

[0061] Cultivation under these conditions makes it difficult for other bacteria (contaminants such as miscellaneous bacteria) to grow, while the Tetragenococcus lactic acid bacteria of the present invention are cultivable, allowing for easy and efficient cultivation of the Tetragenococcus lactic acid bacteria of the present invention. Furthermore, culturing at a salt concentration within the above range prevents the proliferation of non-halotolerant contaminants, while allowing the proliferation rate to be faster than that of salt-tolerant bacteria (halotolerant contaminants), such as halotolerant Staphylococcus bacteria. In other words, even with respect to halotolerant contaminants, the culture can be terminated and the product can be harvested before the proliferation of the contaminants. Cultivation in a medium with a salt concentration of less than 11 w / v% tends to facilitate the proliferation of contaminants, making it difficult to ensure a sufficient yield. Furthermore, culturing in a medium with a salt concentration of more than 18 w / v% makes it more difficult for contaminants to grow, but the culture period required to obtain the required yield is prolonged, potentially resulting in the proliferation of halotolerant contaminants.

[0062] As described above, when cultured in a medium with the above salt concentration, the Tetragenococcus lactic acid bacteria of the present invention can be cultured efficiently and in large quantities even in a simple open-system culture device (which can be sterilized and kept warm) without using special equipment such as a closed-system sterile culture device.

[0063] The culture temperature is preferably 20 to 40° C., more preferably 28 to 37° C. The culture time is about 24 to 120 hours, and the culture may be stirred during culture. The pH of the medium is preferably 5 to 9, more preferably 6 to 7.

[0064] The medium used may contain a nitrogen source and a carbon source.

[0065] The nitrogen source is not particularly limited and examples thereof include soy sauce, miso, meat extract, peptone, gluten, casein, yeast extract, amino acids, etc. The carbon source is also not particularly limited and examples thereof include glucose, koji digestion liquid, rice saccharification liquid, sucrose, starch, powdered sugar, glycerin, etc. Furthermore, in addition to the nitrogen source and carbon source, the culture medium may contain inorganic substances such as inorganic salts such as sodium acetate, magnesium, manganese, and iron, and may also contain vitamins.

[0066] [3] Method for preparing the Tetragenococcus lactic acid bacteria of the present invention: The Tetragenococcus lactic acid bacteria of the present invention can be prepared by culturing them and then sterilizing them. Specifically, after culturing, medium components including salt are removed by centrifugation or other means, followed by washing and purification. If necessary, heat sterilization is performed, and the resulting mixture is then dried and concentrated by freeze-drying, vacuum drying, hot air drying, or other means. In this manner, the Tetragenococcus lactic acid bacteria of the present invention can be prepared after culturing.

[0067] The heat sterilization is not particularly limited, but specifically, autoclave sterilization (121°C, 20 minutes) or a similar sterilization method is preferred.

[0068] [4] Duration of intake of Tetragenococcus lactic acid bacteria: The Tetragenococcus lactic acid bacteria of the present invention are preferably taken continuously for one week or more, and more preferably for two weeks or more.

[0069] [5] Oral composition: The orally ingestible composition of the present invention is a composition for an orally ingestible agent containing the Tetragenococcus lactic acid bacteria of the present invention. This orally ingestible composition is easy to produce because its active ingredient, the Tetragenococcus lactic acid bacteria of the present invention, is easy to culture, does not require expensive production equipment, and does not require complicated production processes, making it an inexpensive, stable, and safe food material (food ingredient). Furthermore, this orally ingestible composition has the ability to increase brain 5-HT, brain DA, or both when taken for a certain period of time.

[0070] Such orally ingestible compositions are not particularly limited, and examples thereof include compositions for antidepressants, compositions for antianxiety agents, dementia drugs, and sleeping pills.

[0071] [5-1] Tetragenococcus lactic acid bacteria: The oral composition of the present invention contains the Tetragenococcus lactic acid bacteria of the present invention as an active ingredient. By using the Tetragenococcus lactic acid bacteria of the present invention, it is possible to increase brain 5-HT, brain DA, or both, while using an inexpensive, stable, and safe food material (food ingredient).

[0072] The oral composition of the present invention is not particularly limited in terms of the content ratio of the Tetragenococcus lactic acid bacteria of the present invention as an active ingredient, and can be appropriately determined. For example, the Tetragenococcus lactic acid bacteria of the present invention can be contained so that approximately 10 billion (equivalent to approximately 2.5 mg) to 5 trillion (equivalent to approximately 1.25 g) of bacteria are ingested per serving. The oral composition of the present invention can be orally taken as a supplement before or after meals to achieve its effects, in addition to being used as a pharmaceutical product such as the above-mentioned antidepressant composition or anti-anxiety composition.

[0073] The oral composition of the present invention may contain a culture, bacterial cells, or bacterial cell components obtained by the method for culturing Tetragenococcus lactic acid bacteria of the present invention.

[0074] [5-2] Other ingredients: The oral composition of the present invention may consist solely of the Tetragenococcus lactic acid bacteria of the present invention (or a composition containing a culture, etc.), but may also contain other components in addition to the Tetragenococcus lactic acid bacteria of the present invention.

[0075] As other ingredients, ingredients that are appropriately blended depending on the application, such as pharmaceuticals, quasi-drugs, foods and beverages, can be used.

[0076] In the case of pharmaceuticals and quasi-drugs, other ingredients may include, for example, excipients, coating agents, binders, bulking agents, disintegrants, surfactants, lubricants, diluents, dispersants, buffers, osmotic pressure adjusters, pH adjusters, emulsifiers, preservatives, stabilizers, antioxidants, colorants, UV absorbers, moisturizers, thickeners, activity enhancers, anti-inflammatory agents, disinfectants, flavoring agents, odor enhancers, etc. Active ingredients or pharmacological ingredients other than the Tetragenococcus lactic acid bacteria of the present invention may also be contained, as long as they do not impair the object of the present invention.

[0077] In the case of foods and beverages, other ingredients can include, for example, sweeteners, acidulants, carbon dioxide gas, inorganic salts, flavorings, fruit juice, vitamins, antioxidants, esters, colorants, emulsifiers, preservatives, seasonings, vegetable extracts, nectar extracts, quality stabilizers, bitterness suppressors, etc. In the case of foods and beverages, active ingredients or pharmacological ingredients other than the Tetragenococcus lactic acid bacteria of the present invention may also be contained, as long as they do not impair the object of the present invention.

[0078] The composition for oral administration of the present invention can be ingested in any form (oral or parenteral). For example, when ingested orally, it may be in a solid form such as a tablet, coated tablet, granule, powder, or capsule, or in a liquid form such as an elixir or syrup.

[0079] [6] Method for producing an orally ingestible composition: The orally ingested composition of the present invention can be produced, for example, by a method comprising a lactic acid bacteria preparation step and a raw material preparation step. This method allows for the easy production of an orally ingested composition. This method has the advantage that Tetragenococcus lactic acid bacteria are salt-tolerant and therefore easy to culture.

[0080] The lactic acid bacteria preparation step is a step of preparing the Tetragenococcus lactic acid bacteria of the present invention. The Tetragenococcus lactic acid bacteria may be prepared by obtaining a seed culture and culturing the seed culture by the method described above, or by purchasing a commercially available lactic acid bacteria (for example, "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.)).

[0081] The raw material preparation step is a step of preparing a raw material for an orally ingested composition by mixing the Tetragenococcus lactic acid bacteria of the present invention prepared in the lactic acid bacteria preparation step with other ingredients as necessary.

[0082] In the case of a solid form such as a tablet, a step for forming the solid form (a forming step) may be adopted after the raw material preparation step.

[0083] [7] Duration of oral administration: The oral composition of the present invention is preferably taken for one week or more, and more preferably for two weeks or more.

[0084] [8] Antidepressant composition: The antidepressant composition of the present invention contains the Tetragenococcus lactic acid bacteria of the present invention. This antidepressant composition is an inexpensive, stable, and safe food material (food ingredient) because its active ingredient, the Tetragenococcus lactic acid bacteria of the present invention, is easy to produce because it is easy to culture, does not require expensive production equipment, and does not require complicated production processes. Furthermore, when ingested for a certain period of time, this antidepressant composition has the ability to increase brain 5-HT, brain DA, or both, and exerts an antidepressant effect.

[0085] The antidepressant composition of the present invention can be produced by adopting the lactic acid bacteria preparation step shown in the method for producing the orally ingested composition of the present invention described above, and other than this step, any conventional method for producing an antidepressant composition can be appropriately adopted.

[0086] [9] Anti-anxiety composition: The anxiolytic composition of the present invention contains the Tetragenococcus lactic acid bacterium of the present invention. This anxiolytic composition is an inexpensive, stable, and safe food material (food ingredient) because its active ingredient, the Tetragenococcus lactic acid bacterium of the present invention, is easy to produce because it can be easily cultured, does not require expensive production equipment, and does not require complicated production processes. Furthermore, this anxiolytic composition has the ability to increase brain 5-HT, brain DA, or both, when ingested for a certain period of time, thereby exerting an anxiolytic effect.

[0087] The anxiolytic composition of the present invention can be produced by employing the lactic acid bacteria preparation step shown in the method for producing the orally ingested composition of the present invention described above, and other than this step, any conventional method for producing anxiolytic compositions can be appropriately adopted. [Example]

[0088] The present invention will be specifically described below based on examples, but the present invention is not limited to these examples.

[0089] Example 1 <Method> (1) Animals used in the experiment: Male ICR mice (8 weeks old, Japan SLC Co., Ltd.) were used and divided into four groups of 10 mice each (7 mice for the normal diet). The mice were pre-bred for one week before use in the experiment. The conditions of the breeding room were as follows: temperature 23±2°C, humidity 50±10%, lighting 12 hours a day (light period 9:00-21:00, dark period 21:00-9:00), food and water were available ad libitum, and the bedding was changed twice a week.

[0090] (2) Feeding of food containing dead bacteria: After one week of feeding, the diet in each group was replaced with the diets described below as test diets 1 to 4, and the rats were fed ad libitum. Test diet 1: Regular diet (Laboratory animal diet CE-2 (manufactured by CLEA Japan)) Hereinafter, the experimental animal feed CE-2 may be simply referred to as "CE-2." Test feed 2: CE-2 plus 1% lactic acid bacteria (1) (test feed containing 1% lactic acid bacteria (1)) sterilized at a sterilization dose of 15 kGy Test feed 3: CE-2 plus 1% lactic acid bacteria (2) (test feed containing 1% lactic acid bacteria (2)) sterilized at a sterilization dose of 15 kGy Test feed 4: CE-2 plus 1% lactic acid bacteria (3) (test feed containing 1% lactic acid bacteria (3)) sterilized at a sterilization dose of 15 kGy

[0091] Lactic acid bacteria (1) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE BP-02318, lactic acid bacteria (2) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03760, and lactic acid bacteria (3) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03761.

[0092] The lactic acid bacteria (1) to (3) were identified and confirmed as "lactic acid bacteria of the genus Tetragenococcus" by the following method. Specifically, a portion of the base sequence of the 16S rRNA gene region was determined, and the species was identified by confirming homology with known gene sequences. Morphological observation and physiological and biochemical property tests confirmed that there were no inconsistencies in the bacteriological properties. In this way, all of the lactic acid bacteria (1) to (3) were confirmed to be "lactic acid bacteria of the genus Tetragenococcus."

[0093] (3) Sample collection: Eight weeks after the start of feeding the killed bacteria-containing diet, blood and brain samples were collected from each mouse. Specifically, the mice were anesthetized with pentobarbital (25 mg / kg) and underwent abdominal surgery under deep anesthesia. Blood was collected from the abdominal vena cava in the presence of heparin and immediately cooled on ice. After all blood was collected, the entire brain was removed and the cerebral cortex was divided on ice. The blood was centrifuged at 12,000 rpm, 4°C, for 10 minutes, and plasma samples were stored at -80°C. The cerebral cortex samples were also stored at -80°C.

[0094] (4) Measurement of brain monoamine levels: 500 μL of 100 μM EDTA·2Na-containing 0.2 M perchloric acid solution containing 50 ng / mL isoproterenol (Iso, Protanol Injection, Kowa) was added to 100 mg of frozen brain sample. The sample was homogenized using a Polytron homogenizer on ice. The homogenized sample was centrifuged at 14,000 rpm at 4°C for 15 minutes. The supernatant was then diluted with 100 μM EDTA·2Na-containing 0.2 M perchloric acid to the appropriate concentration and filtered through a Millex-LH filter (0.45 μm, 4 mm diameter). This filtrate was used as the sample for monoamine measurements.

[0095] Brain monoamines were measured using high-performance liquid chromatography with electrochemical detection (HPLC-ECD) (Eicom Co., Ltd.). The mobile phase was a mixture of 0.05 mM citric acid / sodium acetate buffer (pH 3.5):MeOH = 83:17, supplemented with 190 mg of sodium 1-octanesulfonate and 5 mg of EDTA·2Na, and the flow rate was 0.35 mL / min.

[0096] A 10 μL sample was injected into a high-performance liquid chromatograph (HPLC) and separated using a separation column (EICOMPAKSC-5ODS, 3.0 mm diameter × 150 mm, EICOM, oven temperature 25°C) equipped with a precolumn (PREPAK, 4.0 mm diameter × 5.0 mm, EICOM). The monoamines were detected using an electrochemical detector (EICOM ECD-700KT, working electrode: graphite, reference electrode: silver / silver chloride, applied voltage: +750 mV).

[0097] Monoamine concentrations were measured using a mixture of dopamine (referred to as "DA" in Table 1) hydrochloride (Tokyo Chemical Industry Co., Ltd.), the dopamine metabolite 3,4-dihydroxyphenylacetic acid (referred to as "DOPAC" in Table 1, Sigma-Aldrich), serotonin (referred to as "5-HT" in Table 1, Sigma-Aldrich), and 5-hydroxyindoleacetic acid (referred to as "5-HIAA" in Table 1, Sigma-Aldrich) as the standard solution. A calibration curve was prepared based on the ratio to the internal standard, isopropanol (internal standard ratio). The amount of monoamines in the brain, i.e., the monoamine concentration in the cerebral cortex sample (ng / mg wet tissue) was estimated based on the internal standard ratio in the sample.

[0098] <Result> Table 1 shows that the intake of test feeds 2 to 4 increased brain 5-HT and brain DA levels compared to the intake of test feed 1.

[0099] 5-Hydroxyindoleacetic acid (5-HIAA) is the major metabolic product of 5-HT.

[0100] In Table 1, the 5-HIAA / 5-HT value indicates the metabolic turnover of 5-HT, and the DOPAC / DA value indicates the metabolic turnover of DA. These values ​​did not change with the intake of test diets 2 to 4 compared to the intake of test diet 1, which indicates that 5-HT and DA in the brain increased.

[0101] [Table 1]

[0102] Example 2 <Method> (1) Animals used in the experiment: Male ICR mice (8 weeks old, Japan SLC Co., Ltd.) were used and divided into four groups of five mice per group. The mice were bred for one week before use in the experiment. The conditions of the breeding room were as follows: temperature 23±2°C, humidity 50±10%, lighting 12 hours a day (light period 9:00-21:00, dark period 21:00-9:00), food and water were available ad libitum, and the bedding was changed twice a week.

[0103] (2) Feeding of food containing dead bacteria: After one week of feeding, the diet in each group was replaced with the diets described below as test diets 1 to 4, and the rats were fed ad libitum. Test diet 1: Regular diet (CE-2 (CLEA Japan)) Test feed 2: CE-2 plus 1% lactic acid bacteria (1) (test feed containing 1% lactic acid bacteria (1)) sterilized at a sterilization dose of 15 kGy Test feed 3: CE-2 plus 1% lactic acid bacteria (2) (test feed containing 1% lactic acid bacteria (2)) sterilized at a sterilization dose of 15 kGy Test feed 4: CE-2 plus 1% lactic acid bacteria (3) (test feed containing 1% lactic acid bacteria (3)) sterilized at a sterilization dose of 15 kGy

[0104] Lactic acid bacteria (1) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE BP-02318, lactic acid bacteria (2) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03760, and lactic acid bacteria (3) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03761.

[0105] (3) Behavioral tests: The male ICR mice fed the test diets 1 to 4 were subjected to various behavioral tests (open field test, elevated plus maze test, and forced swimming test).

[0106] (3-1) Open field test: The apparatus used in this test consisted of a square area (50 cm wide x 50 cm deep x 25 cm high) separated by gray walls made of gray, non-reflective polycarbonate. The bottom of the apparatus was divided into 64 identical squares and marked (apparatus: Muromachi Kikai). The experiment began with placing the mouse in a corner of the apparatus and allowing it to freely explore the apparatus for 5 minutes. The amount of walking (number of times it crossed the square marks on the bottom), number of times it stood up, time spent grooming, and number of times it urinated and defecate were recorded. This test was conducted in an environment of 30 lux or less.

[0107] (3-2) Elevated plus maze test: The elevated plus maze (Muromachi Kikai) is an apparatus with a central platform (8 cm x 8 cm) from which two open arms (25 cm long x 8 cm wide x 0.5 cm wall height) and two closed arms (25 cm long x 8 cm wide x 20 cm wall height) form a cross. The entire apparatus is placed 50 cm above the floor. Mice were placed on the central platform of the maze and allowed to freely explore the maze for 5 minutes. Their behavior was videotaped, and the frequency of entries into the open arms, closed arms, and all arms, as well as the time spent in the open arms, central platform, and closed arms, were measured.

[0108] The ratio of the time spent in the open arms to the total time spent in the arms (total time spent in the open arms, central platform, and closed arms) was calculated (time spent in the open arms / time spent in all arms × 100), and is shown in Table 2 below. In Table 2, "n" indicates the number of mice used in the analysis.

[0109] The elevated plus maze test is a widely used test for evaluating anxiety behavior in laboratory animals (mice), and is based on the aversion that mice feel toward high, open spaces and their spontaneous exploratory behavior in new environments. The higher the score, the less anxious the mice are.

[0110] [Table 2]

[0111] (3-3) Forced swimming test: Mice were placed in a plastic cylinder (30 cm high, 20 cm diameter) filled with water (25±1°C, 15 cm deep) and allowed to swim for 15 minutes (apparatus: Merquest). The next day, the mice were placed in the same cylinder again and forced to swim for 7 minutes, and the immobility time during the final 6 minutes was measured. The measurement results are shown in Table 3. In Table 3, "n" indicates the number of mice used in the analysis.

[0112] The forced swimming test is used to test depressive behavior, and mice with a high tendency toward depression will have a longer immobility time (seconds), while mice with a weaker tendency toward depression will have a shorter immobility time (seconds).

[0113] [Table 3]

[0114] <Result> There were no differences in behavior among the groups in the open field test, but differences were observed in behavior among the groups in the elevated plus maze test and forced swimming test.

[0115] As shown in Table 2, in the elevated plus maze test, the percentage of time spent in the open arms increased in the lactic acid bacteria (1) to (3) groups compared to the normal diet group. This means that by ingesting each of the test diets 2 to 4 (lactic acid bacteria (1) to (3)), the animals became less likely to feel anxious, demonstrating an anxiolytic effect.

[0116] As shown in Table 3, in the forced swimming test, the immobility time (seconds) was reduced in the lactic acid bacteria (1) to (3) groups compared to the normal diet group. This means that the intake of each of the test diets 2 to 4 (lactic acid bacteria (1) to (3)) reduced the tendency to depression, demonstrating an antidepressant effect.

[0117] Example 3 <Method> (1) Animals used in the experiment: Male ICR mice (8 weeks old, Japan SLC Co., Ltd.) were used and divided into four groups of five mice per group. The mice were bred for one week before use in the experiment. The conditions of the breeding room were as follows: temperature 23±2°C, humidity 50±10%, lighting 12 hours a day (light period 9:00-21:00, dark period 21:00-9:00), food and water were available ad libitum, and the bedding was changed twice a week.

[0118] (2) Feeding of food containing dead bacteria: After one week of feeding, the diet in each group was replaced with the diets described below as test diets 1 to 4, and the rats were fed ad libitum for four weeks. Test diet 1: Regular diet (CE-2 (CLEA Japan)) Test feed 2: CE-2 plus 1% lactic acid bacteria (1) (test feed containing 1% lactic acid bacteria (1)) sterilized at a sterilization dose of 15 kGy Test feed 3: CE-2 plus 1% lactic acid bacteria (2) (test feed containing 1% lactic acid bacteria (2)) sterilized at a sterilization dose of 15 kGy Test feed 4: CE-2 plus 1% lactic acid bacteria (3) (test feed containing 1% lactic acid bacteria (3)) sterilized at a sterilization dose of 15 kGy

[0119] Lactic acid bacteria (1) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE BP-02318, lactic acid bacteria (2) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03760, and lactic acid bacteria (3) refers to a lactic acid bacterium of the genus Tetragenococcus with accession number NITE P-03761.

[0120] (3) PCR array: Total RNA was extracted from mouse brain samples using a NucleoSpin RNA Plus kit (Takara).

[0121] Specifically, brain samples frozen at -80°C were placed in 1.5 mL tubes and homogenized with the LBP buffer included in the extraction kit. RNA was then extracted using the spin column included in the extraction kit, and the total RNA concentration and purity were confirmed using Nanodrop.

[0122] Next, 1 μg of the extracted total RNA was reverse transcribed into cDNA using the RT2 First Strand Kit (Qiagen), and the reverse-transcribed cDNA sample was then mixed with RT2 SYBR Green qPCR Mastermixes.

[0123] Quantitative PCR was performed using an RT Profiler PCR Array (Qiagen, PAMM-060Z, Mouse Neurotransmitter Receptors). Quantitative PCR analysis was performed using an Applied Biosystems 7300 (Applied Biosystems).

[0124] <Result> Tables 4 and 5 below show the results of PCR array analysis showing changes in expression levels due to the ingestion of lactic acid bacteria (1) to (3). Specifically, Table 4 shows the results of decreases in expression levels due to the ingestion of lactic acid bacteria, and Table 5 shows the results of increases in expression levels due to the ingestion of lactic acid bacteria. The fold change is based on the expression levels of mice (reference mice) that ingested a normal diet (test feed 1), and indicates an increase or decrease relative to the expression levels of the reference mice.

[0125] [Table 4]

[0126] [Table 5]

[0127] As shown in Table 4, the expression levels of "5-HT7 (5-hydroxytryptamine receptor 7)," "Hcrtr2 (Hypocretin (orexin) receptor 2)," and "Tacr1 (Tachykinin receptor 1)" decreased when any of lactic acid bacteria (1) to (3) was ingested.

[0128] The reduction in the expression of these receptors is thought to have the effect of improving symptoms such as depression, anxiety, and insomnia.

[0129] Furthermore, the expression level of "Sstr2" decreased when either lactic acid bacteria (2) or (3) was ingested. Somatostatin is a hormone involved in feeding, and it has been reported that somatostatin-induced feeding behavior is suppressed by somatostatin 2 receptor antagonists. Therefore, it is thought that suppressing the expression of this receptor may be effective in suppressing overeating.

[0130] As shown in Table 5, the expression level of "Adrala (Adrenergic receptor, alpha 1A)" increased when any of lactic acid bacteria (1) to (3) was ingested.

[0131] Since the expression levels of these receptors are enhanced (increased), it is thought that this will have the effect of improving depression and anxiety symptoms.

[0132] Furthermore, as shown in Table 4, the expression level of "5-HT4 (5-hydroxytryptamine receptor 4)" decreased when lactic acid bacteria (2) was ingested. This decrease in the expression level of this receptor is thought to have the effect of improving depression and anxiety symptoms. Furthermore, the expression level of "Sstr2 (Somatostatin receptor 2)" decreased when lactic acid bacteria (2) and (3) were ingested. This decrease in the expression level of this receptor is thought to have the effect of suppressing overeating.

[0133] Furthermore, the expression levels of CHRNA4 (ACH receptor Nicotinic Alpha 4 Subunit) and ADRA2A (Adrenergic receptor, alpha 2A) increased when lactic acid bacteria (3) was ingested. The increased expression levels of these receptors are thought to be effective in improving depression and anxiety symptoms.

[0134] As can be seen from Tables 1 to 5, ingestion of the Tetragenococcus lactic acid bacteria of the present invention increases the 5-HT and DA contents in the brain, exerting antidepressant and anti-anxiety effects. Furthermore, it is also found that the expression levels of certain receptors are enhanced or suppressed.

[0135] More specifically, ingesting the Tetragenococcus lactic acid bacteria of the present invention can prevent or improve mood disorders such as depression and / or anxiety disorders. Specifically, it can enhance the expression of Adrala (adrenergic α1A receptor) and suppress the expression of 5-HT7 (serotonin 7 receptor), Hcrtr2 (orexin receptor 2), and Tacr1 (tachykinin receptor 1), thereby increasing sensitivity to NA (noradrenaline) or attenuating sensitivity to serotonin, orexin, and tachykinin. Furthermore, it is believed that it can activate or deactivate neurotransmission in the brain. [Industrial Applicability]

[0136] The Tetragenococcus lactic acid bacteria of the present invention can be used as an active ingredient for increasing brain 5-HT and / or brain DA. The oral composition of the present invention can be used to increase brain 5-HT and / or brain DA. The antidepressant composition of the present invention can be used to alleviate symptoms of depression. The antianxiety composition of the present invention can be used to alleviate symptoms of anxiety. [Accession number]

[0137] Accession number: NITE BP-02318 Accession number: NITE P-03760 Accession number: NITE P-03761

Claims

1. A lactic acid bacterium of the genus Tetragenococcus having the ability to increase at least one selected from the group consisting of intracerebral serotonin and intracerebral dopamine.

2. The Tetragenococcus lactic acid bacterium described in claim 1, which has the ability to exert at least one of the following functions: enhancing the expression of adrenergic α1A receptor, suppressing the expression of serotonin 7 receptor, suppressing the expression of orexin receptor 2, and suppressing the expression of tachykinin receptor 1.

3. The Tetragenococcus lactic acid bacterium according to claim 1, which is a Tetragenococcus lactic acid bacterium having accession number NITE BP-02318, a Tetragenococcus lactic acid bacterium having accession number NITE P-03760, or a Tetragenococcus lactic acid bacterium having accession number NITE P-03761.

4. An oral composition comprising the Tetragenococcus lactic acid bacterium according to any one of claims 1 to 3.

5. A composition for use as an antidepressant, comprising the Tetragenococcus lactic acid bacterium according to any one of claims 1 to 3.

6. An anti-anxiety composition comprising the Tetragenococcus lactic acid bacterium according to any one of claims 1 to 3.

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